Objective To observe the effects of 1,3-dipropyl-8-cyclopentylxanthine(DPCPX),an adenosine A1 receptor antagonist,on brain neurons damage induced by hypoxia and reoxygenation(H/R),and to elucidate the relevant mechanisms.Methods An in vitro cultured rat cerebral cortical neuronal H/R damage model was established;the effects of DPCPX were detected at final concentrations of 0(control),25,50,100nmol/L on the lactate dehydrogenase(LDH) release from normoxic neurons and H/R neurons which were treated with hypoxia for 8,12,24 hours followed by reoxygenation for 24 hours;the changes of malondialdehyde(MDA) content,activities of xanthine oxidase(XO) and Ca2+-ATPase in H/R neurons which were treated with hypoxia for 12 hours and reoxygenation for 24 hours brought by administration of DPCPX at the concentration of 100nmol/L were also determined by use of specific reagents.Results With addition of 100nmol/L DPCPX,the LDH release from H/R neurons which were treated with hypoxia for 12 hours and reoxygenation for 24 hours was significantly increased compared with that in control group(P

Due to the completion of human genome project and the advent of new technologies, the traditional drug discovery is shifting to genomics-based drug discovery. Target discovery is an important first step in drug discovery pipeline. In this review, we critically introduce the strategies and biology technologies for target discovery, especially focus on the likely impact of new technologies in drug target research and speculate the future trend of target research.

AIM To investigate the effects of the novel compound pivanampeta on the fatty liver induced by cholesterol-feeding in rabbits and quails. METHODS ①24 male rabbits were divided into four groups randomly as following: control group, model group, pivanampet 1 and 5 mg?kg -1 groups. The serum levels of total cholesterol were determined after the rabbits were cholesterol-fed for 12 weeks. The morphological changes of liver were observed. The levels of cholesterol and malonal-dialdehyde and the activities of glutatione peroxidase in the homogenate of liver were also measured.②181 male quails were divided into six groups randomly:control group, model group, Simvastatin 5 mg?kg -1 group, pivanampet 3,6 and 9 mg?kg -1 groups. The serum levels of total cholesterol were determined after the quails had been fed with cholesterol diets for 11 weeks. After 14 weeks part of the animals were killed, the morphological changes of liver were observed. The hepatic coefficient were determined after the remaining quails were cholesterol-feeding for 18 weeks. RESULTS Pivanampet alleviated the liver Steatosis induced by cholesterol-feeding in rabbits and quals. It decreased total cholesterol levels, elevated the activity of glutatione peroxidase in the rabbits liver, and reversed the increasing hepatic coefficient in rabbits and quails. CONCLISION The novel compound Pivanampet can delay the formation of fatty liver by cholesterol-feeding.

ATP sensitive potassium channel(K ATP has been indentified in a variety of tissues and recognized as an important drug target.K ATP channels is composed with a 4∶4 stoichiometry of an inwardly rectifying K + channel(Kir) subunit plus a sulfonylurea receptor(SUR).The characteristics for the SUB2B/Kir 6 1 in vascular are small condutance,ATP insensitivity and activation by added NDP.Therefore,it is refered as NDP dependent K + channel(K NDP ).A lot of endogenous and exogenous vasodilators seem to act through a common pathway by opening K ATP in vascular,which is involved in protein kinase A and C signal transduction pathway.Vascular shows different sensitivity to potassium channel openers(KCO),and the mechanism remains to be determined.In this review,a summary of K ATP in vascular is presented with molecular structure,KCO selectivity to tissue,signal pathway,electrophysiological and pharmacological properties.

?7nAChR, an important neurotransmitter recptor,is w il dly expressed in the central and peripheral neuronal system, which is involved i n neuronal signal transduction and the regulation of physiological functions in the central neuronal system. Several studies have demonstrated that ?7nAChR is identified in non-neuronal cells such as endothelial cells, vascular smooth mus cle cells, bronchial epithelial cells, skin keralinocytes and is involved in the regulation of mitosis,differentiation, organization of the cytoskeleton, cell -cell contact, locomotion and migration. These (in vitro and in vivo) s tudies indicated that ?7nAChR participated in the secretion and release of seve ral bioactivity molecules in endothelial cells, mediated intercellular signal tr ansduction, and regulated angiogenesis. These studies suggested an endogenous ch olinergic target for angiogenesis mediated by endothelial ?7nAChR.

To examine the role and effect of nitric oxide synthase type II (NOS II) in cirrhotic rats, expression of NOS II mRNA was detected by real time RT-PCR. The enzymatic activity of nitric oxide synthase and the circulating levels of NO, systemic and portal hemodynamics and quantification of cirrhosis were measured. Chinese traditional medicine was used to treat cirrhotic rats and the effect of NO was evaluated. Double-blind method was used in experiment. Our results showed the concentration of NO and the enzymatic activity of NOS increased markedly at all stages of cirrhosis and iNOSmRNA was strongly expressed. Meanwhile, the portal-venous-pressure (PVP) and portal-venous-flow (PVF) were significantly increased. NO, NOS and iNOSmRNA were positively correlated to the degree of hepatic fibrosis. Tetrandrine significantly inhibited NO production and the expression of iNOSmRNA. Our results suggested that increased hepatic expression of NOS II is one of the important factors causing cirrhosis and portal hypertension. Tetrandrine can significantly ameliorate cirrhosis and portal hypertension.

There is another factor involving in endothelium dependent relaxation besides NO, which is independent of cGMP, EDHF. Its hyperpolarization mechanism may be related to the open of calcium dependent K + channels(K + Ca). NO, PGI 2,H 2O 2 and cytochrome P450 derived metabolite of arachidonic acid are all the candidates of EDHF. In the normal blood vessels, the influence of EDHF on endothelium dependent relaxation is little. But in some diseases, when the production and effect of NO is disturbed ,the mechanism of EDHF may play a specially important role.

It is well documented that vascular tone is the key determinant of blood vessel resistance and blood flow. But vascular tone could be regulated by modulating the activity of potassium channel directly. Potassium channel openers promote vasodilation by inhibiting the activity of voltage dependent calcium channels and reducing Ca 2+ influx. In this case, inhibition results from membrane hyperpolarisation, which arises due to the stimulation of K + efflux through smooth muscle K + channels. While K + channels are blocked, vasoconstriction could be observed as a result of membrane depolarization, which opens voltage dependent calcium channels. The influx of Ca 2+ can promote smooth muscle contraction by making myosin light chain phosphorylation and arising thick myofilament and thin myofilament relative movements. In this article, the gene structure, current character, Pharmacological and physiological effects of the four subtypes potassium channels are reviewed.

The functions of vascular endothelial cells (VEC) are closely related with the etiology of cardiovascular diseases. The present paper reviews the bioactive substances secreted from endothelial cells and their regulatory effects on the tone of blood vessel wall, on the functions of platelet adhesion and aggregation, on the hemostatic and fibrinolytic systems.

ATP sensitive potassium (K ATP ) channels widely expressed in many tissue and cell types including neurons are heteromultimers of sulfonylurea receptor (SUR) and inward rectifier K + channel (Kir6) subunits associated with 1∶1 stoichiometry as a tetramer (SUR/Kir6) 4. The activity of K ATP channels is modulated by intracellular ATP concentrations. Neuronal K ATP channels are involved in the mediation of glucose sensing and metabolic stress. Under physiological condition, they also possess important pathophysiological functions in acute brain ischemic and chronic neurodegenerative diseases.